Acute encephalopathy in a patient with Dravet syndrome.

Dravet syndrome (severe myoclonic epilepsy in infancy) is an epileptic syndrome with various types of seizures that begin in the first year of life and may result in intellectual impairment. Mutations of the SCN1A gene are the most prevalent genetic cause of Dravet syndrome. In this study, we report a 12-year-old girl with Dravet syndrome carrying an SCN1A mutation, c.2785Cdel (L929del fsX934). She had an episode of status epilepticus and persistent lethargy after 48 h of acute febrile illness that was preceded by an annual flu vaccination. Low voltage activities detected by electroencephalogram and elevated neuron-specific enolase/interleukin-6 concentrations in the cerebrospinal fluid suggested acute encephalopathy. MRI showed abnormalities in the bilateral thalami, cerebellum and brainstem. These abnormalities were protracted over a month. The biochemical and MRI characteristics of this case are different from any known type of encephalopathy, and may suggest a vulnerability of neurons expressing mutant SCN1A in the brain.

A neurodegenerative disorder with early myoclonic encephalopathy, retinal pigmentary degeneration and nephronophthisis.

A female case of developmental arrest, early-onset seizures, retinal pigmentary degeneration, progressive central nervous symptoms and peripheral neuropathy, associated with progressive renal dysfunction, anemia and nephrotic syndrome, was presented. Her epileptic syndrome was possibly an early myoclonic encephalopathy, though neonatal seizures were not evident. Serial cranial MRIs showed progressive brain atrophy and a white matter change. Neuropathological examination revealed a neurodegenerative disease mainly involving the white matter with olivopontocerebellar degeneration. She also had the nephronophthisis-medullary cystic disease complex and an early stage of focal segmental glomerulosclerosis. Her grandaunts had renal diseases, one of whom died of renal failure in adolescence, and her father showed cerebellar symptoms since the middle age. All possible metabolic studies were negative. This case is similar to Senior-Loken syndrome, but distinct in terms of the severe and progressive neurological symptoms, suggestive of a new malignant syndrome with some inherent metabolic derangement affecting both the nervous system and the kidneys.

Thalamocortical development of parvalbumin neurons in normal and periventricular leukomalacia brains.

To clarify disturbances in higher brain functions including cognition and learning disorders in preterm-born children, we investigated the functional development of the cerebral hemisphere, using parvalbumin (PA) immunohistochemistry in human subjects aged from 21 GW to 11 years of age. PA-immunoreactive neurons first appeared in the RNT at 24 GW, spread to the globus pallidus, and then to the VPoL and VPoM. At 38 GW, PA-immunoreactive neurons first appeared in layer 4 of the primary somatosensory cortex and auditory cortex, and comprised a dense band in layers 4 to 5 at 1 month of age. The developmental changes and course of PA expression in the early developmental stage corresponded to development of the thalamocortical connection and then to the functional development of cortical neurons. In preterm cases, PA expression was decreased in the cerebral cortices that corresponded to widespread or diffuse type PVL, but was increased in those with focal type PVL. These results indicate that accelerated expression of PA was induced by extra-uterine stimuli and a reduction of PA reflects the impairment of thalamocortical neurons.

Connatal Pelizaeus-Merzbacher disease associated with the jimpy(msd) mice mutation.

In a patient with connatal Pelizaeus-Merzbacher disease with the same mutation in the proteolipid protein gene as in jimpy(msd) mice the immunohistochemical study of the brain demonstrated deficiencies of myelin and proteolipid protein despite good expression of myelin basic protein. The mechanism of myelination is partly disturbed by the mutation; therefore jimpy(msd) mice can be used as a suitable model for further studies in connatal Pelizaeus-Merzbacher disease.

[Acute necrotizing encephalopathy of childhood: recent advances and future prospects].

Acute necrotizing encephalopathy of childhood (ANE) is a clinicopathological entity recently separated from acute encephalopathy of unknown etiologies. The hallmark of ANE is multiple, bilateral symmetric brain lesions showing edema and necrosis which occur in the bilateral thalami and other specific regions. Since its establishment in 1993-1995, data have further accumulated and have provided additional insight into its pathogenesis. This review summarizes recent achievements on ANE, with reference to issues to be clarified by future studies.

Early expression of proteolipid protein in human fetal and infantile cerebri.

Proteolipid protein (PLP) is the major myelin protein of the central nervous system and is widely believed to play an important structural role in maintaining the myelin compaction. We have studied the early developmental changes of PLP with immunohistochemical methods. Our data demonstrate for the first time a comparable scheme for the development of PLP during myelination in human fetal and infant cerebrum. Expression of PLP was first detected in the pallidothalamic fibers and globus pallidus at 20 weeks; it then extended to the striatum at 28 weeks, pericentral gyri and optic radiation at 35 weeks, and acoustic radiation at 40 weeks. Compared to the expression of myelin basic protein (MBP), another major myelin protein in the central nervous system, the developmental changes of PLP is in the same order as MBP, but the PLP immunoreactivity revealed greater and earlier appearance in the cerebrum than that of MBP in the fetal period. These results imply that PLP is a sensitive and useful marker for early myelination and its disorders.

A comparative magnetic resonance imaging study of the corpus callosum in neurologically normal children and children with spastic diplegia.

To determine the extent of brain damage in children with spastic diplegia, we analyzed the true midsagittal magnetic resonance imaging findings for the corpus callosum in 43 children with spastic diplegia and in 69 neurologically normal children. In the normal children, the thicknesses of the genu, midbody, splenium and the entire corpus callosum were found to increase with age, while the ratios of the thickness of the splenium and of the midbody to the length were constant, regardless of age. Both ratios were significantly reduced in diplegic children and the ratio for the splenium was highly correlated with the extent of motor impairment. Assessment of the morphometric changes in the corpus callosum using magnetic resonance imaging may contribute to the determination of the extent of brain damage in diplegic children.

MRI changes and deficits of higher brain functions in preterm diplegia.

Forty-one preterm children (29 with spastic diplegia and 12 without motor deficits) who had a normal verbal IQ were studied to clarify the clinical significance of neuroanatomical abnormalities disclosed by T1-weighted and T2-weighted magnetic resonance imaging (MRI). Both types of images clearly showed abnormalities in the frontal corona radiata of the children with spastic diplegia, while there were no abnormalities in the children without motor deficits. We compared the T1-weighted imaging findings with deficits of higher brain functions, evaluated by the performance subtests of the Wechsler Intelligence Scale. Thinning of the parietal and/or occipital white matter was noted in children with visuospatial cognitive deficits. Thus, MRI may be helpful in confirming early clinical suspicions of visuospatial cognitive deficits as well as motor deficits in preterm children, especially those with spastic diplegia.

Lack of X inactivation: loss of one X inactivation center in a case with mos45,X,-21, +der(21)t(X;21) (p21.3;p11.2)/46,X,t(X;21) (p21.3;p11.2).

We present a girl with a mos45,X,-21, +der(21)t(X;21) (p21.3;p11.2)/46,X,t(X;21) (p21.3;p11.2) chromosome constitution. The ratio of these cells was 59/26 in phytohemagglutinin (PHA)-stimulated lymphocytes. The 45,X,der(21)t(Xp-;21p+) cells lacked an X inactivation center located at Xq13 on the derivative X chromosome; in these cells, the whole normal X chromosome and the distal part of Xp translocated onto the derivative chromosome 21 were early replicating. She had moderate mental retardation and other findings different from those that occur in the Ullrich-Turner syndrome. Her phenotype may be due to the functional excess of the distal part of Xp on the derivative 21 in 45,X,der(21)t(Xp-;21p+) cells; thus, this might be another type of the "lack of X-inactivation" syndrome.

[A girl with Down syndrome complicated by moyamoya disease and symptomatic atlanto-axial instability].

We reported a girl of Down syndrome with both moyamoya disease and spinal cord compression due to atlanto-axial instability. At the age of 3 years, she presented with muscle weakness of gradual onset, and could not walk without support. On admission, at the age of 6, she presented with spastic paraparesis with predominance on the right side. To explain her neurological manifestations, we performed cranial MRI first, and found multiple infarctions with predominance on the right hemisphere, the occlusive changes of internal carotid and middle cerebral arteries, and signal void flow signs in basal ganglia, which suggested moyamoya disease. Although diagnosis of moyamoya disease was confirmed by cranial angiography, discrepancy between clinical manifestations (right-side dominant spasticity) and MRI findings (right-side dominant infarctions) could not be explained. Thereafter, we performed cervical MRI, which showed severely compressed lesions with predominance on the right side, corresponding to her clinical manifestations. It is essential to perform not only cranial but also cervical MRI for a patient with Down syndrome presenting neurological complications.

[MRI and autopsy findings in the brain of a child born with extreme prematurity].

We present the brain autopsy and MRI findings in a four-year-old boy who was born at 23 weeks of gestational age and 700 gram of birthweight and experienced an episode of cardiac arrest at 10 months of age. Neuropathological study showed the findings compatible with cardiac arrest syndrome, the gliosis or neuronal loss of extensive cerebral lesions including the cerebral white matter and cortex, basal ganglia, cerebellum and hippocampus, and large ulegyric formation in the bilateral parietal and occipital lobes, as well as the periventricular leukomalacia, which characterize hypoxic-ischemic insult in the brain of preterm infant. MRI performed eight months before his death demonstrated prominent atrophy and periventricular and parenchymal hyperintensity of the bilateral occipital lobes consistent with the above pathological findings.

The use of magnetic resonance imaging in diagnosing infantile neuroaxonal dystrophy.

We used MRI to investigate the brains of four children ranging from 3 to 10 years of age with infantile neuroaxonal dystrophy. T2-weighted imaging revealed characteristic findings of marked cerebellar atrophy and diffuse hyperintensity of the cerebellar cortex. At autopsy, one child had extensive astrogliosis and neuronal loss with shrinkage of the cerebellar cortex, in addition to typical widespread changes of neuroaxonal dystrophy. The characteristic hyperintensity of the cerebellar cortex on T2-weighted imaging probably is secondary to the extensive gliosis and shrinkage of the cerebellar cortex. These cerebellar findings on MRI may permit early diagnosis of infantile neuroaxonal dystrophy.

[Neonatal tuberous sclerosis: report of a case studied by cranial MRI].

We reported longitudinal cranial MRI studies of a neonate with tuberous sclerosis who presented convulsive seizures on the first day after birth. Cortical tubers were not detected on MRI performed at the age of 1 month, but became evident at 18 months after birth. This finding might reflect the pathological difference between the amount of myelin around the cortical tuber and other white matter lesions, which increased with age. A heterotopic islet was shown as partially stratiform appearance on MRI. This result suggests that the structure of the heterotopic islet might be heterogeneous.

Neuroradiological findings in children with congenital myotonic dystrophy.

We studied seven children with congenital myotonic dystrophy, aged 2.1-8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neonatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow-up computed tomography scans taken at intervals of one to six years. Also, in T2-weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxial episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopment outcome and the extent of the periventricular hyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia.

[A case of acute encephalopathy with symmetrical low density areas in the thalami on CT; serial CT and MRI findings].

A 5-year-old girl was admitted to our hospital because of fever, vomiting, diarrhea, convulsion and disturbance of consciousness. She was diagnosed as having acute encephalopathy, which is characterized by the symmetrical low density area in the thalami on CT. Serial MRI findings revealed the bleeding with edema in the thalami, and multifocal lesions with prolonged T1 and T2 relaxation time in the acute phase of the illness. Multifocal lesions were no longer found two months later. The sequential changes on the images about the bleeding in the thalami were not confirmed by simultaneous CT scans. The findings of the bleeding in the thalamic lesion are consistent with those of an autopsy report previously described and indicate the vascular involvement in the thalami in acute encephalopathy, which is characterized by the symmetrical thalamic lesions with the characteristic finding of low density on CT scans.

Normative data and the effect of correction for prematurity on test scores in the psychomotor development of extremely low birthweight infants.

This study was concerned with the problem how we should allow for gestational age at birth when evaluating psychomotor development in extremely low birthweight (ELBW) infants. The consequences of the use of corrected and uncorrected developmental test scores as to the degree of prematurity were studied in 27 consecutive ELBW children who had been categorized as being normal on neurological and psychological testing at 5 1/2 years. The present study provides evidence that the overall trend of psychomotor development in normal ELBW children is not accelerated, but is guided by maturation of the central nervous system. This study also suggests that there are no significant differences in the predictive value of corrected and uncorrected DQ scores after 2 years of age with respect to IQ scores at 5 1/2 years.

Neurologic sequelae and MRI in low-birth weight patients.

Periventricular hyperintensity was detected using long repetition and echo time on spin-echo magnetic resonance imaging in 24 of 32 children with birth weights less than 2,500 gm. Functionally, 11 children were normal, 6 mildly handicapped, 7 moderately handicapped, and 8 severely handicapped. The functional handicaps were correlated to the degree of periventricular hyperintensity observed on magnetic resonance imaging when periventricular hyperintensity was divided into 4 grades; therefore, the extent of periventricular hyperintensity observed on magnetic resonance imaging has been proved to be of value in the clinical assessment of low-birth weight infants and children and may contribute to the prediction of later functional deficits.